Pharmaceutical compositions exist to optimize the delivery of a pharmaceutical active to its site of release. Compliance has become a major problem, particularly for pediatric and geriatric patients or certain patients who already have difficulty in swallowing solid medications. Oral liquid formulations such as suspension pharmaceutical compositions have been developed as an alternative to tablets in order to circumvent this problem; however, suspensions are often thermodynamically unstable and may result in aggregation and sedimentation during storage. Problems are often encountered because the accuracy of the dose depends on the even distribution of particles in the suspensions at the time the preparations are administered to the patients.
It is often desirable to have a tablet that disintegrates and disperses rapidly in the mouth without requiring any water intake other than the normal flow of saliva. Such tablets are easier for the elderly and children who often have difficulty in chewing or swallowing large capsules or tablets.
Patient convenience leads to compliance with the prescribed dosing regimen and, as a consequence, to enhanced therapeutic benefit. Orally disintegrating tablets are a viable alternative for convenient administration of drugs to patients who have difficulty in swallowing.
Rapidly disintegrating oral pharmaceutical compositions should have a pleasant taste, good mouth feel and should dissolve quickly. It is generally recognized that rapidly disintegrating tablets must dissolve in the mouth within 60 secs, more preferably in less than 30 secs. Besides, they can be taken at any time or place without the need for chewing or drinking water or any other liquid. When placed in mouth, these tablets disintegrate in a few seconds, resulting in quick absorption of the drug substances through the buccal and oesophageal mucosa, resulting in faster bioavailability of active ingredients with minimal first pass metabolism.
Widely known technologies that have been developed in the formulation of fast disintegrating tablets employ techniques of freeze-drying, direct compression and moulding.
Several fast dissolving/disintegrating drug delivery systems have been developed to assist pediatric and geriatric patients. Cardinal Healthcare markets Zydis™, which is a freeze-dried tablet (U.S. Pat. Nos. 4,642,903, 5,188,825, 5,631,023, 5,827,541 and 5,976,577) having an oral dissolution time of 2 to 5 seconds. The freeze-drying technology has limitations due to factors such as time, costly equipment and processing conditions. Besides, tablets formulated by this technology lack physical resistance and heed special handling and packaging.
Cima labs markets Orasolv™ (U.S. Pat. No. 5,178,878) and Durasolv™ (U.S. Pat. Nos. 6,221,392 and 6,024,981) where Orasolv™ is an effervescent direct compression tablet, that disperses in mouth's saliva with the aid of almost hardly noticeable effervescence and dissolves in less than one minute, leaving the coated drug powder. The unpleasant flavor of the drug is addressed by coating of the drug powder and effervescence. The major disadvantage of Orasolv™ is its mechanical strength due to light compression. Durasolv™ is a recently introduced direct compression tablet having higher mechanical strength than Orasolv™ due to the use of higher compaction pressures during tabletting.
U.S. Patent Application No. 20030175339 to Bunick, Frank, J.; et al. discloses a process for preparing chewable or disintegrable tablet comprising an active, a hydrate and a water-swellable excipient (disintegrant). The process comprises applying energy (heat) to tablets to achieve softening effect. It also discloses the preparation of tablets by direct compression. The tablets have a friability of less than 2%.
U.S. Patent Application No. 20050019398 to Kothari, Sanjeev; et al. discloses granules for preparing flash-melt oral pharmaceutical compositions. The formulation comprises a super disintegrant, a dispersing agent, a distributing agent and a binder. The disclosed composition optionally contains sweetening and flavouring agents. The reference discloses that the granules are prepared without the aid of solvents and are stable. Said application also discloses that the tablets disintegrate in mouth under 25 seconds. Calcium silicate is used as the dispersing agent.
Generally mannitol is commonly used as an excipient (diluent) in the manufacture of rapidly disintegrating pharmaceutical compositions because of its negative heat of solution and sweetness. According to Khankari et al. (U.S. Pat. No. 6,221,392 and U.S. Pat. No. 6,024,981) the use of directly compressible mannitol with large particle size in rapidly disintegrating pharmaceutical compositions presents problems since they do not solubilize quickly. This contributes to a mouth sensation of gritty or sandy texture of the mannitol as the pharmaceutical composition disintegrates. Khankari et al. have adopted the process of incorporating non-directly compressible fillers, including mannitol, which have fine particle size. By suitable adjustments in composition properties like flow and compressibility, Khankari et al, have been able to produce tablets by direct compression also.
None of the described prior art teaches a solution for the problems related to the use of filler like mannitol having large particle size where the problem is organoleptic characteristic like mouth feel due to the gritty or sandy texture of the filler, when prepared by a compression method.
It is, therefore, an object of the present invention to improve upon limitations in the prior art. Accordingly, the present invention provides an improved orally dissolving pharmaceutical formulation, which is able to dissolve rapidly in the mouth of the patient, with minimum of grit or other organoleptic unpleasant sensations.